3,165 research outputs found
Will Corporate Tax Consolidation improve Efficiency in the EU ?
The European Commission favours the introduction of a consolidated corporate tax base to overcome the distortions arising from the existing system of separate accounting. The blueprints for consolidation are simulated with the applied general equilibrium model CORTAX. We show that the benefits of a common consolidated tax base are limited due to two weaknesses. Formula apportionment, which is needed to allocate the consolidated taxable profits across jurisdictions, creates for MNEs new tax planning possibilities to exploit tax rate differentials in the European Union. In addition, it triggers tax competition as the incentives for member states to attract foreign investment by reducing their tax rates are enforced. The second weakness arises from the unlevel playing field, which is introduced if only part of the firms chooses to participate in the consolidation. The gains from consolidation can be fully grasped if it is obliged for all firms and accompanied by harmonisation of the tax rate
Sperm structure and motility in the eusocial naked mole-rat, Heterocephalus glaber: a case of degenerative orthogenesis in the absence of sperm competition?
<p>Abstract</p> <p>Background</p> <p>We have studied sperm structure and motility in a eusocial rodent where reproduction is typically restricted to a single male and behaviourally dominant queen. Males rarely compete for access to the queen during her estrus cycle, suggesting little or no role for sperm competition.</p> <p>Results</p> <p>Our results revealed an atypical mammalian sperm structure with spermatozoa from breeding, subordinate and disperser males being degenerate and almost completely lacking a "mammalian phylogenetic stamp". Sperm structure is characterized by extreme polymorphism with most spermatozoa classified as abnormal. Sperm head shapes include round, oval, elongated, lobed, asymmetrical and amorphous. At the ultrastructural level, the sperm head contains condensed to granular chromatin with large open spaces between the chromatin. Nuclear chromatin seems disorganized since chromatin condensation is irregular and extremely inconsistent. The acrosome forms a cap (ca 35%) over the anterior part of the head. A well defined nuclear fossa and neck with five minor sets of banded protein structures are present. The midpiece is poorly organized and contains only 5 to 7 round to oval mitochondria. The flagellar pattern is 9+9+2. A distinct degenerative feature of the tail principal piece is the absence of the fibrous sheath. Only 7% motile spermatozoa were observed which had exceptionally slow swimming speeds.</p> <p>Conclusion</p> <p>In this species, sperm form has simplified and degenerated in many aspects and represents a specialised form of degenerative orthogenesis at the cellular level.</p
A Multiple Classifier System Identifies Novel Cannabinoid CB2 Receptor Ligands
open access articleDrugs have become an essential part of our lives due to their ability to improve peopleâs
health and quality of life. However, for many diseases, approved drugs are not yet available
or existing drugs have undesirable side effects, making the pharmaceutical industry strive to
discover new drugs and active compounds. The development of drugs is an expensive
process, which typically starts with the detection of candidate molecules (screening) for an
identified protein target. To this end, the use of high-performance screening techniques has
become a critical issue in order to palliate the high costs. Therefore, the popularity of
computer-based screening (often called virtual screening or in-silico screening) has rapidly
increased during the last decade. A wide variety of Machine Learning (ML) techniques has
been used in conjunction with chemical structure and physicochemical properties for
screening purposes including (i) simple classifiers, (ii) ensemble methods, and more recently
(iii) Multiple Classifier Systems (MCS). In this work, we apply an MCS for virtual screening
(D2-MCS) using circular fingerprints. We applied our technique to a dataset of cannabinoid
CB2 ligands obtained from the ChEMBL database. The HTS collection of Enamine
(1.834.362 compounds), was virtually screened to identify 48.432 potential active molecules
using D2-MCS. This list was subsequently clustered based on circular fingerprints and from
each cluster, the most active compound was maintained. From these, the top 60 were kept,
and 21 novel compounds were purchased. Experimental validation confirmed six highly
active hits (>50% displacement at 10 ÎźM and subsequent Ki determination) and an
additional five medium active hits (>25% displacement at 10 ÎźM). D2-MCS hence provided a
hit rate of 29% for highly active compounds and an overall hit rate of 52%
The use of oscillatory signals in the study of genetic networks
The structure of a genetic network is uncovered by studying its response to
external stimuli (input signals). We present a theory of propagation of an
input signal through a linear stochastic genetic network. It is found that
there are important advantages in using oscillatory signals over step or
impulse signals, and that the system may enter into a pure fluctuation
resonance for a specific input frequency.Comment: 46 pages, 5 figures. Submitted to PNAS on May 27th 2004. The paper is
under consideratio
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